Monitoring of blood concentrations of isoniazid and rifampicin in different dosage forms

doi:10.3969/j.issn.1004-583X.2024.11.005

Abstract

Abstract:

Objective To measure blood concentrations of isoniazid (INH) and rifampicin (RFP) in different dosage forms. Methods From July 20, 2022 to November 30, 2022, 123 patients with active tuberculosis hospitalized in the Second Department of Tuberculosis of Kunming Third People's Hospital were included. They were randomly divided into injection group ( $n$ =64) and oral group ( $n$ =59). Both groups were given ethambutol and pyrazinamide. Additionally, the injection group was given RFP injection and INH injection, and the oral group was given RFP capsules and INH tablets. On the 7th day of treatment, blood samples were collected 2 hours and 24 hours after treatment, and the blood concentrations of INH and RFP in the two groups were detected by high performance liquid chromatography.Results There were no significant differences in age, sex, body mass index, treatment history, tuberculosis culture and lesion between the two groups (P>0.05). After 2 hours of medication on the 7th day of treatment, blood concentration of RFP and the proportion of patients with a targeted blood concentration of RFP were significantly higher in the injection group than those of the oral group (P<0.05). The proportions of patients with blood concentration of RFP<8 mg/L and 8-24 mg/L in the injection group was significantly lower than that of the oral group, and the proportion of patients with blood concentration of RFP>24 mg/L was significantly higher than that of the oral group (P<0.05). Multivariate linear regression model analysis showed that age was the influencing factor of blood concentration of INH. The older the age, the lower the blood concentration of INH ( $F$ =7.774, P=0.006).Conclusion The blood concentration of RFP injections is significantly higher than that of oral RFP capsules. For patients with severe or oral treatment of gastrointestinal reactions, RFP injections can be given priority to improve the clinical efficacy. INH is recommended to be given according to body weight, aiming to increase the blood concentration and strengthen the blood concentration monitoring.

Key words: tuberculosis, rifampicin, isoniazid, different dosage forms, blood concentration

CLC Number:

Wang Lin, Wan Rong, Liu Sha, Liu lei, He Jing, Tang Libin, Li Mingwu. Monitoring of blood concentrations of isoniazid and rifampicin in different dosage forms[J]. Clinical Focus, 2024, 39(11): 989-992.

Add to citation manager EndNote|Ris|BibTeX

URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.11.005

https://huicui.hebmu.edu.cn/EN/Y2024/V39/I11/989

Figures/Tables 7

Tab.1 General information between groups

组别	例数	年龄 (岁)	BMI (kg/m²)	性别[例(%)]		治疗史[例(%)]		结核菌培养[例(%)]		病灶[例(%)]
组别	例数	年龄 (岁)	BMI (kg/m²)	男	女	初治	复治	阳性	阴性	空洞	浸润	粟粒
口服组	59	42.7±13.5	23.0±3.6	35(59.3)	24(40.7)	48(81.4)	11(18.6)	22(37.3)	37(62.7)	7(11.9)	49(83.1)	3(5.0)
注射组	64	43.2±13.3	22.5±1.8	41(64.1)	23(35.9)	55(85.9)	9(14.1)	20(31.3)	44(68.7)	9(14.1)	49(76.6)	6(9.3)
$t$ /χ²值		0.184	-0.980	2.246		0.526	0.234	0.339	0.587	0.324	1.097	0.790
P值		0.854	0.329	0.134		0.468	0.629	0.561	0.444	0.569	0.295	0.374

Tab.1 General information between groups

组别	例数	年龄 (岁)	BMI (kg/m²)	性别[例(%)]		治疗史[例(%)]		结核菌培养[例(%)]		病灶[例(%)]
组别	例数	年龄 (岁)	BMI (kg/m²)	男	女	初治	复治	阳性	阴性	空洞	浸润	粟粒
口服组	59	42.7±13.5	23.0±3.6	35(59.3)	24(40.7)	48(81.4)	11(18.6)	22(37.3)	37(62.7)	7(11.9)	49(83.1)	3(5.0)
注射组	64	43.2±13.3	22.5±1.8	41(64.1)	23(35.9)	55(85.9)	9(14.1)	20(31.3)	44(68.7)	9(14.1)	49(76.6)	6(9.3)
$t$ /χ²值		0.184	-0.980	2.246		0.526	0.234	0.339	0.587	0.324	1.097	0.790
P值		0.854	0.329	0.134		0.468	0.629	0.561	0.444	0.569	0.295	0.374

Tab.2 The blood concentrations of INH and RFP at 2 hours and 24 hours of medication on the 7th day of treatment between groups

组别	例数	用药2 h后		用药24 h后
组别	例数	INH(mg/L)	RFP(mg/L)	INH(mg/L)	RFP(mg/L)
口服组	59	2.18(1.47, 3.77)	21.34(5.97, 38.64)	1.40(0.86, 3.17)	3.07(1.85, 9.49)
注射组	64	2.21(1.10, 4.52)	47.95(33.49, 80.16)	1.28(0.93, 2.51)	5.26(1.89, 10.84)
$Z$ 值		-0.013	-5.501	-0.856	-0.330
P值		0.990	<0.001	0.392	0.741

Tab.2 The blood concentrations of INH and RFP at 2 hours and 24 hours of medication on the 7th day of treatment between groups

组别	例数	用药2 h后		用药24 h后
组别	例数	INH(mg/L)	RFP(mg/L)	INH(mg/L)	RFP(mg/L)
口服组	59	2.18(1.47, 3.77)	21.34(5.97, 38.64)	1.40(0.86, 3.17)	3.07(1.85, 9.49)
注射组	64	2.21(1.10, 4.52)	47.95(33.49, 80.16)	1.28(0.93, 2.51)	5.26(1.89, 10.84)
$Z$ 值		-0.013	-5.501	-0.856	-0.330
P值		0.990	<0.001	0.392	0.741

Tab.3 The blood concentrations of INH and RFP in different dosage forms at 2 hours of medication on the 7th day of treatment

组别	例数	INH[例(%)]			RFP[例(%)]
组别	例数	<3 mg/L	3~6 mg/L	>6 mg/L	<8 mg/L	8~24 mg/L	>24 mg/L
口服组	59	38(64.4)	15(25.4)	6(10.2)	17(28.8)	19(32.2)	23(39.0)
注射组	64	41(64.1)	17(26.6)	6(9.3)	5(7.8)	3(4.7)	56(87.5)
χ²值		0.002	0.021	0.022	9.219	15.825	31.452
P值		0.968	0.886	0.882	0.002	<0.001	<0.001

Tab.4 INH and RFP reaching target concentration after 2 hours of medication on the 7th day of treatment

组别	例数	用药2 h后达目标浓度[例(%)]
组别	例数	INH	RFP
口服组	59	21(35.6)	42(71.2)
注射组	64	23(35.9)	59(92.2)
χ²值		0.002	9.219
P值		0.968	0.002

Fig.1 Blood concentrations-age scatter plot

Tab.5 Multiple linear regression analysis results

自变量	偏回归系数	标准误	标准化偏回归系数	$t$ 值	P值
年龄	-0.043	0.063	-0.176	-2.788	0.006

Tab.5 Multiple linear regression analysis results

自变量	偏回归系数	标准误	标准化偏回归系数	$t$ 值	P值
年龄	-0.043	0.063	-0.176	-2.788	0.006

Fig.2 Blood concentrations-age standardization plot

References 20

[1]	World Health Organization. Global tuberculosis report 2023[EB/OL].[2023-11-07]. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/globaltuberculosis-report-2023.
[2]	李亮, 李琦, 许绍发, 等. 结核病治疗学[M]. 北京: 人民卫生出版社, 2013:22-30.
[3]	Alsultan A, Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis:An update[J]. Drugs, 2014, 74(8):839-854.
[4]	王黎霞, 成诗明, 周林, 等. 中华人民共和国卫生行业标准肺结核诊断: WS 288-2017[J]. 中国感染控制杂志, 2018, 17(7):642-652.
[5]	国卫办疾控函[2020]279号. 中国结核病预防控制工作技术规范(2020版)[S]. 北京: 中华人民共和国国家卫生健康委员会办公厅,2020-04-02.
[6]	李明武, 赖明红, 马萌, 等. 不同剂型利福平投药后血药浓度的监测结果分析[J]. 中国防痨杂志, 2019, 41(6):645-649.
[7]	李明武, 万荣, 朱惠琼, 等. 不同剂型异烟肼血药浓度监测结果分析[J]. 中华临床医师杂志(电子版), 2019, 13(6):440-443.
[8]	张亮, 钱智磊, 陆磊, 等. 同时测定血浆 INH、AcINH、RFP 和 PZA 的高效液相色谱法建立及其在肺结核患者中的应用[J]. 山东医药, 2015, (48):23-26.
[9]	钱智磊, 张亮, 周秋云, 等. HPLC 法测定结核病患者血浆中异烟肼、吡嗪酰胺、利福平和左氧氟沙星的质量浓度[J]. 西北药学杂志, 2014, 29(6):578-581.
[10]	焉学英, 张酉生. 利福平注射液治疗初治肺结核强化期疗效观察[J]. 临床肺科杂志, 2011, 16(7):1119-1120.
[11]	龚惠莉. 利福平注射液比较利福平胶囊治疗初治空洞型肺结核疗效分析[J]. 现代预防医学, 2012, 39(2):498-499.
[12]	朱春梅. 利福平注射液与利福平胶囊治疗初治空洞型肺结核疗效分析[J]. 临床肺科杂志, 2011, 16(2):219+222.
[13]	李明武, 马萌, 张瑞雨, 等. 异烟肼、利福平不同剂型对肺结核病患者的临床疗效[J]. 昆明医科大学学报, 2019, 40(1):105-108.
[14]	张艳. 利福平治疗肺结核的血药浓度监测及对患者免疫功能的影响分析[J]. 贵州医药, 2020, 44(4):560-562.
[15]	郭少晨, 朱慧, 郭超, 等. 909例结核病患者一线抗结核药物血药浓度监测结果分析[J]. 中国防痨杂志, 2018, 40(7):744-749.
[16]	张冰, 西娜, 陈明, 等. 274例结核病患者抗结核药物血药浓度分析及其药物安全性探究[J]. 中国药物应用与监测, 2023, 20(2):90-94.
[17]	周俊, 吕小会, 刘元, 等. 三种抗结核药物血药浓度在个体及药物间的差异研究[J]. 中国防痨杂志, 2017, 39(5):482-487.
[18]	孙晓方, 严文, 任斐, 等. 442例异烟肼血药浓度监测结果分析[J]. 中国防痨杂志, 2015, 37(11):1136-1140.
[19]	孙学智, 石丽稳, 赵丽, 等. 糖尿病对异烟肼和利福平血药浓度的影响[J]. 武汉大学学报(医学版), 2023, 44(6):764-767.
[20]	张亮, 冯枭, 林霏申, 等. 异烟肼血药浓度的影响因素分析[J]. 药学与临床研究, 2018, 26(6):413-416.